Implantable, refillable infusion device and septum replacement kit

ABSTRACT

An implantable infusion device includes a lightweight, inert housing which contains an infusate for administration to a patient, and an enclosed, gas-impermeable variable volume chamber which contains a pressure source, such as propellant, mechanical spring, or the like. The variable volume chamber may be in the form of a rigid-walled expandable bellows structure or a nonstretchable flexible bag and is attached to the housing so as not to obstruct the entry port for introduction of infusate. The infusate is delivered from the device via a catheter in response to expansion of the variable volume chamber against the volume of infusate in the housing. A separate bolus injection port is provided which allows infusate to be safely introduced directly into the catheter and overrides the controlled pressure-driven delivery. The lightweight housing may include integrally formed needle stops and suture fastening loops.

[0001] This application is a continuation of U.S. application Ser. No.09/481,298, filed Jan. 11, 2000, now pending.

TECHNICAL FIELD

[0002] The invention relates to implantable infusion devices forcontrollable in vivo delivery of drugs to a patient.

BACKGROUND OF THE INVENTION

[0003] Implantable infusion devices provide a patient with an in vivosource of a drug to be administered, in a device which permitscontrolled delivery of the drug over a predetermined time period.Certain drugs, such as, for example, chemotherapy drugs and opioids, maybe most effective if administered at a constant dose rate, instead of atdiscrete intervals.

[0004] A typical infusion device or pump includes a hermetically sealedouter housing which holds a vapor pressure fluid or other means forexerting a compressive force on a compressible or flexible inner drugreservoir which communicates with a drug delivery port. Alternatively,the drug may be disposed in the outer housing, with a propellantdisposed in the inner housing. When the outer housing is filled with thedrug, the propellant in the inner housing is compressed and changesstate from a vapor to a liquid, thereby recharging the driving mechanismof the device. In still other embodiments, the outer housing may bedivided into two chambers separated by a liquid-impermeable diaphragm.One chamber contains the drug and includes a drug delivery port, and theother chamber contains a propellant or spring member for exerting aforce against the diaphragm so as to expel the drug through the deliveryport.

[0005] The infusion device must meet numerous requirements for safetyand efficacy. For example, the housing material must not react with bodyfluids or with the drugs and propellants inside the housing. Further,the membrane or flexible barrier between the chambers must not leak andmust be impermeable to gas-phase fluids so as to prevent contaminationof the drug with the propellant. Since the device is designed forimplantation into a patient, great care must be taken to prevent anyleakage of either the drug or the propellant into the patient's body. Inaddition, the device is desirably as small and lightweight as possibleso as to cause minimum invasive trauma, discomfort and disfigurement tothe patient, yet sufficiently large to provide a useful therapeuticdosage of the drug being administered and minimize the frequency withwhich the device must be recharged. It is desirable to make the pumprefillable so that it need not be surgically removed and replaced whenthe drug is depleted. However, refillability of the pump requires a portwhich is either outside of the skin or transcutaneously accessiblewithout introducing infection or risking the release of an excessive andpotentially harmful amount of the drug into the patient. Also, in thosedevices in which a propellant is contained within a flexible bag whichexpands and contracts in response to changes in the propellant pressure,it is necessary to ensure that introduction of the drug to the drugreservoir surrounding the propellant bag is not impeded by the presenceand location of the bag in the reservoir and/or does not puncture orpinch the bag. Thus, it may be necessary to affix the propellant chamberor bag to the housing so as to avoid such problems. There is theadditional problem of ensuring that the drug reservoir can be fullydepleted and refilled, for optimum efficiency of the device.

[0006] Administration of a desired dosage of a drug over a period oftime may require a controllable, constant flow of the drug from thedevice. However, as the drug is depleted from the reservoir, or if theforce exerted on the drug reservoir cannot be controlled, a constantdose rate may be difficult to sustain.

[0007] U.S. Pat. No. 3,840,009 to Michaels et al. discloses a vaporpressure drug delivery device which has two chambers separated by aflexible wall or bladder. The outer chamber contains a drug to beadministered to a patient, and the inner chamber contains a pressurefluid which expands to conform to the shape of the outer chamber,thereby enabling expulsion of substantially all of the drug within theouter chamber. The pressure fluid is maintained at a positive pressureat the temperature at which the device is used, so that no externalpower source is required.

[0008] U.S. Pat. No. 5,167,633 to Mann et al. discloses a medicationinfusion pump in which a constant pressure is exerted on a liquidmedication to be administered. The pump includes a pressure reservoir inthe form of a hollow enclosure with at least one flexible wall forcontaining a pressure fluid. The medication to be administered isoutside of the pressure reservoir. The pressure fluid undergoes a phasechange from a liquid to a vapor so as to expel the drug from the pump.The Mann et al. device is maintained at a negative pressure at thetemperature of use to avoid leakage of medication from the pump into thepatient.

[0009] U.S. Pat. No. 5,514,103 to Srisathapat et al. discloses amedication infusion pump including a drug reservoir and a pressure fluidreservoir which are separated by a movable wall or flexible bag. Thepressure fluid reservoir includes a spacer therein to preventcontraction of the pressure fluid reservoir below a minimum volume whichis slightly greater than the liquid phase volume of the pressure fluid,so that a portion of the pressure fluid always remains in a vapor phase.As a result, even when the drug reservoir is completely filled, thepressure fluid is not entirely in the liquid phase. Thus, additionalenergy to reinstate a vapor phase is not required.

[0010] U.S. Pat. No. 3,951,147 to Tucker et al. discloses a refillableimplantable infusate pump in which a bellows containing a drug iscontained within a housing which is filled with a pressure fluid orpropellant. The Tucker et al. pump includes a filtering chamber toensure removal of debris from the infusate drug prior to its delivery tothe patient.

[0011] U.S. Pat. No. 5,045,064 to Idriss discloses a constant pressureimplantable pump which employs shape-memory metal bands around areservoir containing a fluid to be infused. The bands compress thereservoir containing the fluid to be infused, thereby eliminating theneed for a propellant.

[0012] U.S. Pat. No. 5,395,324 to Hinrichs et al. discloses an infusionpump having a primary entry port leading to a drug reservoir, a separatebolus port leading to a bolus chamber, and means for ensuring that thebolus chamber is not inadvertently filled with the drug intended for theprimary drug reservoir.

[0013] U.S. Pat. No. 5,769,823 to Otto discloses an implantable infusionpump which comprises a plastic housing, a bellows chamber enclosing apropellant, and two separate resilient plastic bags enclosing aninfusate. The bags are surrounded by glycerin or the like which bindswith any propellant passing through the bellows wall into the housing,thereby preventing passage of the propellant through the housing intothe patient.

[0014] U.S. Pat. No. 5,575,770 to Melsky et al. discloses an implantableinfusion pump having a valve-actuated bolus delivery chamber.Inadvertent administration of an overdose to the patient through thebolus delivery chamber is prevented by a design which requires the useof a side-access delivery needle, which is inserted through a pair ofsepta which are spaced apart to define a bolus chamber. The tip of theneedle extends beyond the lower septum and depresses a lever to actuatethe normally-closed valve. The side opening of the needle is disposedbetween the septa in the bolus chamber for delivery of the bolus dose tothe bolus chamber. The design prevents erroneous dose delivery byrequiring the simultaneous opening of the valve with delivery of thedrug into the bolus using a side-access delivery needle.

[0015] It would be advantageous to provide an implantable infusion pumpwhich is of simple construction and operation, made of lightweightmaterials, inexpensive to manufacture, efficient in the delivery ofmedicine, and easy to refill.

SUMMARY OF THE INVENTION

[0016] According to one aspect of the invention, there is provided animplantable infusion device, comprising a housing having an annularportion with an inner wall defining an interior region having a widthdimension ID and extending along a central axis, a bottom portionextending from the annular portion and spanning a first end of theinterior region, and a top portion extending from the annular portionand spanning a second end of the interior region and being opposite thebottom portion, the interior region being substantially closed. Thedevice further includes a closed fluid-impermeable hollow bellowsextending from one of the top and bottom portions of the housing anddefining a variable volume region therein and having a plurality ofserially coupled annular members extending between top and bottomportions of the bellows. Junctions of the coupled annular members arecoupled with flexures. The bellows has a maximum outer width dimensionD′ where D′ is less than D. The portion of the housing from which thebellows extends includes a substantially planar annular peripheralportion disposed about a central portion. A pressure source is containedwithin the variable volume region of the bellows. The bellows isdisposed within the interior region of the housing and rigidly coupledto the portion of the housing from which it extends. The annularmembers, of the bellows are spaced apart from the annular portion of thehousing. The housing includes a recharging fluid flow path from pointsexternal to the housing to a region adjacent to the central portion ofthe portion of the housing from which the bellows extends. The housingfurther defines a fluid exit flow path extending from the region betweenthe bellows and the annular portion of the housing to points external tothe housing.

[0017] The device further includes a pierceable, self-sealing septumdisposed in the recharging fluid flow path and may further include arecharging fluid reservoir disposed along the recharging fluid flowpath. The septum may be removable from the housing.

[0018] The device further includes at least one of a flow restrictor anda filter disposed along the fluid exit flow path.

[0019] In one embodiment, the housing is made of a gas-impermeablematerial, and the bellows which encloses the pressure source is made ofa substantially rigid, gas-impermeable material. In a preferredembodiment, the bellows is hermetically sealed.

[0020] The pressure source comprises one or more of the group consistingof multiple-phase fluids, springs, shape memory metal alloys, Belvillewashers, and compressible materials. In one embodiment, a multiple-phasefluid propellant is present in at least one of a liquid phase and a gasphase within the variable volume region of the bellows as a function ofambient temperature. Conversion of the propellant fluid from a liquidphase to a gas phase increases the volume displaced by the bellows inthe interior region of the housing, thereby exerting a force on a fluidexternal to the bellows in the housing so as to provide a substantiallyconstant flow rate of the fluid through the fluid exit flow path.

[0021] In a preferred embodiment, the propellant is disposed in thevariable volume region of the bellows at a pressure which is not lessthan atmospheric pressure at ambient temperature.

[0022] In one embodiment, the central portion of the bellows is offsetfrom the plane of the annular peripheral portion of said bellows. Acentral region of the portion of the housing from which the bellowsextends is correspondingly offset from the plane of the annular portionof the housing. The offset central region of the housing substantiallynests within the offset central portion of the bellows.

[0023] In one embodiment, the housing and bellows are cylindrical.

[0024] The device can further include a separate bolus port in fluidcommunication with the fluid exit flow path. The bolus port can includea pair of septa which are spaced apart to define a bolus reservoirtherebetween. A side-access delivery needle having an opening near thecenter of its length is required to delivery a bolus dose of theinfusate to the bolus reservoir.

[0025] In one preferred embodiment, the bellows extends from the topportion of the housing. In another preferred embodiment, the bellowsextends from the bottom portion of the housing.

[0026] According to another aspect of the invention, there is providedan implantable infusion device, comprising a housing having an annularportion with an inner wall defining an interior region having a widthdimension D and extending along a central axis, a bottom portionextending from the annular portion and spanning a first end of theinterior region, and a top portion extending from the annular portionand spanning a second end of the interior region, the top portion beingopposite the bottom portion, the interior region being substantiallyclosed. The device further includes a closed fluid-impermeable hollowbellows disposed about a variable volume region and having a top member,a bottom member, and a plurality of serially coupled annular membersextending therebetween. Junctions of the coupled annular members arecoupled with flexures. The bellows has a maximum outer width dimensionD′ where D′ is less than D. At least one of the top and bottom membersincludes a substantially planar annular peripheral portion disposedabout a central portion. A pressure source is contained within thevariable volume region of the bellows, and the bellows is disposedwithin the interior region of the housing with one of the top and bottommembers facing and rigidly coupled to a corresponding portion of thehousing. The annular members of the bellows are spaced apart from theannular portion of the housing. The housing includes a recharging fluidflow path from points external to the housing to a region adjacent tothe central portion of one of the top and bottom members of the bellows.The region of coupling between the housing and the bellows defines afluid dispersal flow path from the region adjacent to the centralportion of the coupled member of the bellows to a region between theannular members of the bellows and the annular portion of the housing.The housing further defines a fluid exit flow path extending from theregion between the bellows and the annular portion of the housing topoints external to the housing.

[0027] In one embodiment, a central portion of at least one of the topand bottom members of the bellows is offset from the plane of theannular peripheral portion of the top and bottom members of the bellows.A central region of the portion of the housing which is coupled to thebellows is correspondingly offset from the plane of the annular portionof the housing, so that the offset central region of the portion of thehousing which is coupled to the bellows nests within the central portionof the coupled portion of the bellows.

[0028] In one preferred embodiment, the bellows is coupled to the topportion of the housing. In another preferred embodiment, the bellows iscoupled to the bottom portion of the housing.

[0029] According to still another aspect of the invention, there isprovided a septum replacement kit for an enclosed device which is sealedwith a septum, wherein the enclosed device defines a fluid reservoir, afluid flow inlet and a fluid flow outlet. The kit comprises acompressible septum adapted to sealingly engage in the fluid flow inletof the reservoir, and a septum installation tool adapted to compress theseptum to a nominal insertion size, maintain the nominal insertion sizeof the septum prior to installation of the septum, and install theseptum in the fluid flow inlet of the reservoir.

[0030] The septum installation tool preferably comprises a tubularmember adapted for insertion into the fluid flow inlet of the reservoir,an opening in the tubular member for insertion and retention of theseptum therein, and a plunger member disposable in the tubular memberfor expulsion of the septum from the tubular member. Insertion of theseptum into the tubular member compresses the septum. Expulsion of theseptum from the tubular member into the fluid inlet reservoir permitsthe septum to expand to fill in and seal the fluid inlet reservoir.

[0031] The septum is preferably made of a pierceable, self-sealingelastomeric or rubber-like material.

[0032] These and other objects and advantages of the invention will inpart be obvious and will in part appear hereinafter. The inventionaccordingly comprises the apparatus possessing the construction,combination of elements and arrangement of parts which are exemplifiedin the following detailed disclosure, the scope of which will beindicated in the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] For a fuller understanding of the nature and objects of thepresent invention, reference should be made to the following detaileddescription taken in connection with the accompanying drawings, inwhich:

[0034]FIG. 1 is a perspective view of an infusion device according tothe invention;

[0035]FIG. 2 is a schematic diagram of the device which illustrates itsstructure and principles of operation;

[0036]FIG. 3 is a sagittal view of the device of FIG. 1;

[0037]FIG. 4 is a sagittal view of an alternate design of the device, inwhich the sideport bolus port is located at an angle on a peripheraledge of the device;

[0038]FIG. 5 is a sagittal view of a replaceable septum in a deviceaccording to the present invention;

[0039]FIGS. 6A-6C illustrate a septum replacement kit and the steps forinstalling a replacement septum with a septum replacement tool; and

[0040]FIGS. 7A-7B illustrate a bolus port safety feature which preventsinadvertent administration of an overdose of drug to the patient throughthe bolus injection port.

[0041] Like features in the drawings are indicated with like numerals.

DETAILED DESCRIPTION OF THE DRAWINGS

[0042] The infusion device of the present invention combines severalfeatures known in the art in a novel and unobvious way. The device has arelatively low profile, as shown in FIGS. 1, 3 and 4, and is remarkablein several aspects. First, the device can be housed in a lightweight,biologically inert material which need not be hermetically sealed. Thisis because, unlike most prior art infusion devices, the pressure sourcein the claimed device, which can be a propellant fluid, a mechanicalspring or the like, or a combination of such elements, is contained in aseparate enclosed container within the housing of the device, and theinfusate, or drug to be administered, is outside the containercontaining the pressure source.

[0043] The container for the pressure source ideally is in the form of avariable volume container, such as a metal bellows or a flexible bag orenvelope. However, unlike an expandable balloon bag, the variable volumecontainer has a defined maximum and minimum volume. The infusate isadministered to the patient from the device upon expansion of thevariable volume container within the interior region of the housinguntil the variable volume container effectively fills the interiorvolume of the housing, at which point the infusate is substantiallydepleted.

[0044] The device can also be transcutaneously recharged with infusatewithout requiring that the device be removed from the patient.Recharging the infusate effectively recharges the pressure source bycompressing the variable volume container to its minimum volume andcreating pressure which is used to expel the infusate from the device.

[0045] The device also includes a separate bolus injection port forintroduction of a bolus dose to the patient which bypasses the pressuresource-driven delivery of the infusate from the principal reservoir ofthe device. Pierceable, self-sealing septa through which infusate can beinjected into the device are located in the primary and bolus ports ofthe device for convenient introduction and containment of infusate andbolus injections.

[0046] In addition, because the housing can be made of a lightweightmaterial, such as plastic, many features, such as fluid flow channels,compartments, needle stops and suture loops, can be integrated into thehousing during its manufacture, which can be accomplished by molding orother low-cost, high-volume manufacturing processes.

[0047]FIG. 1 shows a perspective view of the infusion device 10according to the invention. FIG. 2 illustrates in schematic form thebasic structure and principle of operation of the device. FIG. 3 is adetailed sectional view of the device of FIG. 1 along a sagittal(vertical longitudinal) axis. FIG. 4 is a sagittal view of an alternatedesign of the device, in which the side bolus port is located at anangle from a top edge of the device. FIG. 5 is a sagittal view of areplaceable septum for the device. FIGS. 6A-6C illustrate a septumreplacement kit and a method of using it to remove a worn septum andreplace it with a fresh septum. FIGS. 7A-7B illustrate a bolus safetyfeature which prevents the inadvertent administration of a principaldose of the drug to be infused through the bolus injection port.

[0048] The device 10 is contained within a housing 12 made of alightweight, durable, and biologically inert material, such as plastic.The housing is conveniently formed of an upper housing 12 a and a lowerhousing 12 b, which are joined with an o-ring 14 between them to createa fluid-impermeable seal. The halves of the housing can be joined by,for example, ultrasonic or thermal welding, solvent bonding, or otheradhesive-based bonding.

[0049] The housing of the device defines an interior region which formsa principal reservoir 16 for the infusate 18, which is typically a drugto be administered over a period of time at a constant low dose to apatient into which the device has been surgically implanted. Theinfusate is introduced into the principal reservoir via a principalentry port 20, which is sealed with a pierceable, self-sealing septum22. The infusate is delivered from the principal reservoir to a catheter24 via exit flow path 25, which may contain at least one of a filter 26and a flow restrictor 28.

[0050] In one preferred embodiment of the invention, the device caninclude a separate restrictor chamber in the upper half 12 a. Thisseparate restrictor chamber permits the use of interchangeablerestrictors for establishing different infusate flow rates.

[0051] Delivery of the infusate from the principal reservoir is drivenby a pressure source P contained within a variable volume enclosedchamber 30, which may be attached to the housing, preferably to theupper housing 12 a, as detailed more fully below. The pressure sourcemay be a multiple-phase fluid which expands from a liquid phase to a gasphase with increasing temperature, thereby increasing in volume andpushing against the walls of the variable volume container to enlargeit, thereby decreasing the volume of the principal reservoir 16 andexpelling the infusate therein from the device. Alternatively, thepressure source can be a mechanical device, such as a spring or othercompressible member, or a shape-memory metal alloy. A combination of apropellant fluid and a compressible mechanical member may also be usedto obtain a desired infusate delivery rate from the device. Themechanical member may, but need not, exert a constant force throughoutits stoke range.

[0052] If a propellant fluid is used as the pressure source within thevariable volume chamber, it is desirable to have the minimum volume ofthe chamber be greater than the liquid volume of the propellant fluid,so that the propellant fluid must always exist in the chamber in bothliquid and gas phases. In addition, it is desirable to select apropellant fluid which is at a pressure of not less than one atmosphereat ambient temperature, so that at the temperature of use (typicallynominal body temperature of the patient) the propellant is at a pressurewhich is even higher than one atmosphere of pressure. This allows thesurgeon to prime and operate the device at ambient temperature in orderto verify its performance prior to implantation of the device in thepatient, thereby eliminating the need to warm the device and theinfusate to body temperature. In addition, such a positive pressuredevice eliminates the risk that outside air or gases will be drawn intothe device during storage of the device.

[0053] The inert plastic housing containing the infusate 12 may, butneed not, be hermetically sealed. The housing, if made of a moldable oreasily formed material, may include, for example, integrally formedneedle stops 32, 34 for the primary and bolus injection sites, as wellas one or more integrally formed suture loops 36 for passage ofanchoring sutures therethrough.

[0054] The variable volume chamber 30 is desirably a substantiallyrigid, gas-impermeable bellows structure, as illustrated in FIGS. 3 and4, or other similar rigid-walled or spring-driven structure whichoccupies a volume which approximates the volume of the principalreservoir 16. Preferred materials for the bellows chamber include metalsand plastics. An important feature of the variable volume chamber is itswidth dimension or diameter D′ relative to the diameter D of thehousing. It is necessary to have D′ be less than D, so that the bellowswalls are spaced from the housing walls, but only by so much as willallow the bellows walls to move freely within the housing. It isdesirable to have the bellows walls as close as possible to the housingwalls so that maximum displacement of infusate can be achieved bymovement of the bellows in the reservoir. However, drag of the bellowswalls on the housing walls must be avoided. Thus, it is desirable tohave the variable volume chamber centered in the principal reservoir formaximum volume and avoidance of drag and so that the distance D-D′ issufficient to avoid such drag.

[0055] Although the device and bellows are illustrated as cylindrical ina preferred embodiment, they may have any convenient shape.

[0056] Another important consideration is that the variable volumechamber must not be located so that it obstructs the principal entryport for infusate when the principal reservoir is empty and the variablevolume chamber is at its maximum volume. In a preferred embodiment, thevariable volume chamber 30 may be attached to the housing so as todefine a fluid flow path between the variable volume chamber and thehousing. Alternatively, the chamber 30 and housing 12 may be designed toshare a common wall which may be channeled to provide fluid flow pathsalong the interface between the housing and the chamber 30. In stillanother alternate embodiment, the bellows may be freely located in theinterior region of the housing. In this embodiment, the free bellows isdesirably held away from the infusate entry port by standoffs extendingfrom the bellows or from the infusate entry port.

[0057] To ensure as low a profile as possible for the device, it isdesirable to construct the housing so that the central portion of one orboth of its top and bottom portions, along with corresponding centralportions of the top and bottom members of the bellows, is offset ordepressed from the nominal plane of the central portions as shown inFIGS. 3 and 4 to form a nested structure. The infusate entry port nestswithin a recessed central portion of the bellows. Although only the topportions of the housing and bellows are shown as nested in FIGS. 3 and4, the bottom portions of the housing and bellows could also be nestedto further reduce the height of the device. Reductions in the volume ofthe infusate chamber 30 reduce the amount of infusate that can beadministered and increase the frequency with which the chamber 30 mustbe recharged if drug delivery is to take place over an extended period.However, the pressure source can be selected so as to maximize deliveryfrom a given volume.

[0058] The device includes a separate bolus injection port 38, whichincludes a bolus entry port 40 sealed with a pierceable, self-sealingseptum 42, and leading to a bolus reservoir 44, which is in fluidcommunication with the fluid exit flow path 25 and delivery catheter 24,yet downstream of the filter 26 and flow restrictor 28. Infusateintroduced into the bolus port goes directly into the delivery catheterand bypasses the controlled release provided by the action of thepressure source and variable volume chamber on the infusate in theprincipal reservoir.

[0059] Both the principal infusate entry port and the bolus injectionport may include sensing devices known in the art which assist thepatient and medical staff in locating the devices transdermally so thatadditional infusate can be introduced to the device without the need forexternal palpation or surgical removal of the device.

[0060] The life of an implantable infusion device such as thosedescribed herein is determined in large part by the life of the septumthrough which the infusate is introduced. Use of a self-sealingmaterial, such as an elastomer, silicone rubber or similar material, forthe septum allows the septum to reseal after it has been pierced with aneedle. However, even self-sealing materials lose some elasticity aftera certain number of uses and must be replaced to ensure that no infusateleaks out of the device.

[0061] Septum life, and thus infusion device life, can be optimized bycareful selection of the septum material and the dimensions of theseptum and the septum chamber in the device. This is shown in FIG. 5.The ratio of the opening dimension of the septum chamber (B) to thewidth of the septum chamber (A) must be such that the entire septumvolume can fit within the chamber opening B when the septum iscompressed, and such that the chamber width A adequately compresses theseptum to provide satisfactory puncture life. The selection of amaterial for the septum is also an important consideration, as itshardness, as measured by a durometer, must allow for adequatecompression of the septum during insertion without comprising puncturelife. The height of the septum chamber (C) must be sufficient to permitthe compressed septum to fill the chamber and still be sufficientlyaxially compressed to achieve the desired puncture life.

[0062] A septum replacement kit allows the surgeon to replace a wornseptum without surgically removing the device from the patient. Such akit is illustrated in FIGS. 6A-6C. FIG. 6A shows a septum 22, which istypically in the form of a cylindrical or square plug of height H andwidth W. The septum is preferably made of a compressible, resilient,penetrable, self-sealing material, such as a rubber or elastomer. FIG.6B shows the septum lodged in a tubular member 46, which is sized to fitinto the entry port 20, having width B, of the infusion device 12. Theseptum is easily compressed sufficiently to be lodged into the tubularmember 46, and a plunger 48 is used to dislodge the septum from thetubular member into the septum chamber 50, which has width A and heightC, after it is inserted into the entry port 20, as shown in FIG. 6C. Theseptum is radially compressed in the chamber to form a penetrable seal.The plunger and tubular member can then be withdrawn.

[0063] Removal of a worn septum can be accomplished by inserting a sharpinstrument into the septum to cut it into sections that can then beremoved from the septum chamber with tweezers or other suitableinstrument.

[0064] Although the FIGS. illustrate use of the septum replacement kitfor replacing the primary septum 22, the kit can also be used to replacethe bolus septum 42 in the bolus injection port 40.

[0065] In addition, the device may include safety filling devices knownin the art to ensure that the patient and medical staff can distinguishbetween the primary entry port and the bolus injection port so as toavoid inadvertent administration of relatively large doses intended tobe administered over time to the patient. When an implanted infusionpump is to be refilled, it may be difficult to determine whether arefill needle is positioned to enter the principal infusate port or thebolus port. Entry of the refill needle into the wrong port for the dosebeing administered can result in a patient receiving an excessive doseof the drug and therefore must be prevented.

[0066] A bolus safety feature in accordance with the present inventionis shown and described in connection with FIGS. 7A-7B. FIG. 7Aillustrates the two infusate ports in a typical implantable infusionpump according to the invention. The device includes a principal, orcenter, access port (1) for administration of infusate into the device,and a bolus access port (2) for administration of a bolus injectiondirectly to the patient. The center access port (1) includes a singleseptum, below which is disposed an infusate reservoir R. To fill thecenter access port (1), a refill needle having a hole in the tip, asshown in (1), is required.

[0067] In contrast, the side bolus access port (2) includes two septawhich are spaced apart to define an infusate reservoir R between them.The top septum in the bolus access port (2) secures the delivery needlein place and provides a seal to prevent leakage of the bolus dose oncethe needle is removed from the bolus port. The bottom septum blocks theopening in the tip of a standard refill needle, shown in (1), shouldsuch a needle be inserted into the bolus port. Only a special needlewith a side-access opening near the center of its length, as shown in(2), instead of at or near the tip, as shown in (1), can be used to fillthe bolus port.

[0068]FIG. 7B shows the result of using a standard delivery needle inthe bolus port. The standard delivery needle includes an opening at itstip and no opening in the side. The opening in the tip will be blockedby the lower septum when the needle is inserted into the bolus port, andno infusate will be delivered.

[0069] This design of the center and bolus ports in the device of theinvention ensures that no bolus dose can be administered inadvertentlyto a patient, because only a bolus (side-access opening) needle can beused in the bolus port. If a standard delivery needle is accidentallyinserted into the bolus port, no infusate can be delivered, and thesurgeon can see immediately that the wrong needle is being toed, withoutadministering any harmful dose to the patient.

[0070] Because certain changes may be made in the above apparatuswithout departing from the scope of the invention herein disclosed, itis intended that all matter contained in the above description or shownin the accompanying drawings shall be interpreted in an illustrative andnot a limiting sense.

1. An implantable infusion device, comprising: A. a housing having (a)an annular portion with an inner wall defining an interior region havinga width dimension D and extending along a central axis, (b) a bottomportion extending from said annular portion and spanning a first end ofsaid interior region, and (c) a top portion extending from said annularportion and spanning a second end of said interior region, said topportion being opposite said bottom portion, wherein said interior regionis substantially closed; and B. a closed fluid-impermeable hollowbellows extending from one of the top and bottom portions of the housingand defining a variable volume region therein and having a plurality ofserially coupled annular members extending between top and bottomportions of the bellows, wherein junctions of said coupled annularmembers are coupled with flexures, said bellows having a maximum outerwidth dimension D′ where D′ is less than D, wherein the portion of thehousing from which the bellows extends includes a substantially planarannular peripheral portion disposed about a central portion, wherein apressure source is contained within said variable volume region of saidbellows, and wherein said bellows is disposed within said interiorregion of said housing and rigidly coupled to said portion of thehousing from which the bellows extends, whereby said annular members ofsaid bellows are spaced apart from said annular portion of said housing,wherein said housing includes a recharging fluid flow path from pointsexternal to said housing to a region adjacent to said central portion ofsaid portion of said housing from which the bellows extends, and whereinsaid housing further defines a fluid exit flow path extending from theregion between said bellows and said annular portion of said housing topoints external to said housing.
 2. An implantable infusion deviceaccording to claim 1, further comprising a pierceable, self-sealingseptum disposed in said recharging fluid flow path.
 3. An implantableinfusion device according to claim 2, wherein the septum is removablefrom the housing.
 4. An implantable infusion device according to claim1, further comprising a recharging fluid reservoir disposed along saidrecharging fluid flow path.
 5. An implantable infusion device accordingto claim 1, further comprising at least one of a flow restrictor and afilter disposed along said fluid exit flow path.
 6. An implantableinfusion device according to claim 1, wherein said housing is made of agas-impermeable material.
 7. An implantable infusion device according toclaim 1, wherein the pressure source comprises one or more of the groupconsisting of multiple-phase fluids, springs, shape memory metal alloys,Belville washers, and compressible materials.
 8. An implantable infusiondevice according to claim 1, wherein a multiple-phase fluid propellantis present in at least one of a liquid phase and a gas phase within saidvariable volume region of said bellows as a function of ambienttemperature, wherein conversion of the propellant from a liquid phase toa gas phase increases the volume displaced by the bellows in theinterior region of the housing, thereby exerting a force on a fluidexternal to said bellows in said housing so as to provide asubstantially constant flow rate of said fluid through said fluid exitflow path.
 9. An implantable infusion device according to claim 8,wherein said propellant is disposed in said variable volume region ofsaid bellows at a pressure which is not less than atmospheric pressureat ambient temperature.
 10. An implantable infusion device according toclaim 1, wherein said bellows is made of a substantially rigid,gas-impermeable material.
 11. An implantable infusion device accordingto claim 1, wherein said bellows is hermetically sealed.
 12. Animplantable infusion device according to claim 1, wherein said centralportion of said bellows is offset from the plane of said annularperipheral portion of said bellows.
 13. An implantable infusion deviceaccording to claim 12, wherein a central region of said portion of saidhousing from which the bellows extends is correspondingly offset fromthe plane of the annular portion of the housing, wherein the offsetcentral region of the housing substantially nests within said offsetcentral portion of said bellows.
 14. An implantable infusion deviceaccording to claim 1, wherein the housing and bellows are cylindrical.15. An implantable infusion device according to claim 1, furthercomprising a separate bolus port in fluid communication with said fluidexit flow path.
 16. An implantable infusion device according to claim15, further comprising a pair of septa disposed in said bolus port,wherein the septa are spaced apart to define a bolus reservoirtherebetween, wherein a delivery needle having an opening near thecenter of its length is required to deliver infusate to the bolusreservoir.
 17. An implantable infusion device according to claim 1,wherein the bellows extends from the top portion of the housing.
 18. Animplantable infusion device according to claim 1, wherein the bellowsextends from the bottom portion of the housing.
 19. An implantableinfusion device, comprising: A. a housing having (a) an annular portionwith an inner wall defining an interior region having a width dimensionD and extending along a central axis, (b) a bottom portion extendingfrom said annular portion and spanning a first end of said interiorregion, and (c) a top portion extending from said annular portion andspanning a second end of said interior region, said top portion beingopposite said bottom portion, wherein said interior region issubstantially closed; and B. a closed fluid-impermeable hollow bellowsdisposed about a variable volume region and having a top member, abottom member, and a plurality of serially coupled annular membersextending therebetween, wherein junctions of said coupled annularmembers are coupled with flexures, said bellows having a maximum outerwidth dimension D′ where D′ is less than D, wherein at least one of saidtop and bottom members includes a substantially planar annularperipheral portion disposed about a central portion, wherein a pressuresource is contained within said variable volume region of said bellows,and wherein said bellows is disposed within said interior region of saidhousing with one of said top and bottom members facing and rigidlycoupled to a corresponding portion of said housing, whereby said annularmembers of said bellows are spaced apart from said annular portion ofsaid housing, wherein said housing includes a recharging fluid flow pathfrom points external to said housing to a region adjacent to saidcentral portion of one of said top and bottom members of said bellows,and wherein the region of coupling between said housing and said bellowsdefines a fluid dispersal flow path from said region adjacent to saidcentral portion of said coupled member of said bellows to a regionbetween said annular members of said bellows and said annular portion ofsaid housing, and wherein said housing further defines a fluid exit flowpath extending from the region between said bellows and said annularportion of said housing to points external to said housing.
 20. Animplantable infusion device according to claim 19, further comprising apierceable, self-sealing septum disposed in said recharging fluid flowpath.
 21. An implantable infusion device according to claim 20, whereinthe septum is removable from the housing.
 22. An implantable infusiondevice according to claim 19, further comprising a recharging fluidreservoir disposed along said recharging fluid flow path.
 23. Animplantable infusion device according to claim 19, further including atleast one of a flow restrictor and a filter disposed along said fluidexit flow path.
 24. An implantable infusion device according to claim19, wherein said housing is made of a gas-impermeable material.
 25. Animplantable infusion device according to claim 19, wherein the pressuresource comprises one or more of the group consisting of multiple-phasefluids, springs, shape memory metal alloys, Belville washers, andcompressible materials.
 26. An implantable infusion device according toclaim 19, wherein a multiple-phase fluid propellant is present in atleast one of a liquid phase and a gas phase within said variable volumeregion of said bellows as a function of ambient temperature, whereinconversion of the propellant from a liquid phase to a gas phaseincreases the volume displaced by the bellows in the interior region ofthe housing, thereby exerting a force on a fluid external to saidbellows in said housing so as to provide a substantially constant flowrate of said fluid through said fluid exit flow path.
 27. An implantableinfusion device according to claim 26, wherein said propellant isdisposed in said variable volume region of said bellows at a pressurewhich is not less than atmospheric pressure at ambient temperature. 28.An implantable infusion device according to claim 19, wherein saidbellows is made of a substantially rigid, gas-impermeable material. 29.An implantable infusion device according to claim 19, wherein saidbellows is hermetically sealed.
 30. An implantable infusion deviceaccording to claim 19, wherein said central portion of at least one ofthe top and bottom members of said bellows is offset from the plane ofsaid annular peripheral portion of said top and bottom members of saidbellows.
 31. An implantable infusion device according to claim 30,wherein a central region of said portion of said housing coupled to thebellows is correspondingly offset from the plane of the annular portionof the housing, wherein the offset central region of said portion of thehousing coupled to the bellows substantially nests within said centralportion of the coupled portion of said bellows.
 32. An implantableinfusion device according to claim 19, wherein the bellows is coupled tothe top portion of the housing.
 33. An implantable infusion deviceaccording to claim 19, wherein the bellows is coupled to the bottomportion of the housing.
 34. An implantable infusion device according toclaim 19, wherein the fluid dispersal flow path includes regions ofincreased surface contact area in the coupled region between the housingand the bellows.
 35. An implantable infusion device according to claim19, wherein the housing and bellows are cylindrical.
 36. An implantableinfusion device according to claim 19, further comprising a separatebolus port in fluid communication with said fluid exit flow path.
 37. Animplantable infusion device according to claim 36, further comprising apair of septa disposed in said bolus port, wherein the septa ape spacedapart to define a bolus reservoir therebetween, wherein a deliveryneedle having an opening near the center of its length is required todeliver infusate to the bolus reservoir.
 38. An implantable infusiondevice, comprising: A. a housing having (a) an annular portion with aninner wall defining an interior region having a width dimension D andextending along a central axis, (b) a bottom portion extending from saidannular portion and spanning a first end of said interior region, and(c) a top portion extending from said annular portion and spanning asecond end of said interior region, said top portion being opposite saidbottom portion, wherein said interior region is substantially closed; B.a closed fluid-impermeable hollow bellows extending from one of the topand bottom portions of the housing and defining a variable volume-region therein and having a plurality of serially coupled annularmembers extending between top and bottom portions of the bellows,wherein junctions of said coupled annular members are coupled withflexures, said bellows having a maximum outer width dimension D′ whereD′ is less than D, wherein the portion of the housing from which thebellows extends includes a substantially planar annular peripheralportion disposed about a central portion, wherein a pressure source iscontained within said variable volume region of said bellows, andwherein said bellows is disposed within said interior region of saidhousing and rigidly coupled to said portion of the housing from whichthe bellows extends, whereby said annular members of said bellows arespaced apart from said annular portion of said housing, wherein saidhousing includes a recharging fluid flow path from points external tosaid housing to a region adjacent to said central portion of saidportion of said housing from which the bellows extends, and wherein saidhousing further defines a fluid exit flow path extending from the regionbetween said bellows and said annular portion of said housing to pointsexternal to said housing; and C. a separate bolus port in fluidcommunication with said fluid exit flow path, wherein said bolus portincludes a pair of septa disposed therein and spaced apart to define abolus reservoir therebetween, wherein a delivery needle having anopening near the center of its length is required to deliver infusate tothe bolus reservoir.
 39. An implantable infusion device, comprising: A.a housing having (a) an annular portion with an inner wall defining aninterior region having a width dimension D and extending along a centralaxis, (b) a bottom portion extending from said annular portion andspanning a first end of said interior region, and (c) a top portionextending from said annular portion and spanning a second end of saidinterior region, said top portion being opposite said bottom portion,wherein said interior region is substantially closed; B. a closedfluid-impermeable hollow bellows disposed about a variable volume regionand having a top member, a bottom member, and a plurality of seriallycoupled annular members extending therebetween, wherein junctions ofsaid coupled annular members are coupled with flexures, said bellowshaving a maximum outer width dimension D′ where D′ is less than D,wherein at least one of said top and bottom members includes asubstantially planar annular peripheral portion disposed about a centralportion, wherein a pressure source is contained within said variablevolume region of said bellows, and wherein said bellows is disposedwithin said interior region of said housing with one of said top andbottom members facing and rigidly coupled to a corresponding portion ofsaid housing, whereby said annular members of said bellows are spacedapart from said annular portion of said housing, wherein said housingincludes a recharging fluid flow path from points external to saidhousing to a region adjacent to said central portion of one of said topand bottom members of said bellows, and wherein the region of couplingbetween said housing and said bellows defines a fluid dispersal flowpath from said region adjacent to said central portion of said coupledmember of said bellows to a region between said annular members of saidbellows and said annular portion of said housing, and wherein saidhousing further defines a fluid exit flow path extending from the regionbetween said bellows and said annular portion of said housing to pointsexternal to said housing; and C. a separate bolus port in fluidcommunication with said fluid exit flow path, wherein said bolus portincludes a pair of septa disposed therein and spaced apart to define abolus reservoir therebetween, wherein a delivery needle having anopening near the center of its length is required to deliver infusate tothe bolus reservoir.
 40. A septum replacement kit for an enclosed devicewhich is sealed with a septum, wherein the enclosed device defines afluid reservoir, a fluid flow inlet and a fluid flow outlet, the kitcomprising: a compressible septum adapted to sealingly engage in thefluid flow inlet of the reservoir; and a septum installation tooladapted to compress the septum to a nominal insertion size, maintainsaid nominal insertion size of said septum prior to installation of theseptum, and install the septum in the fluid flow inlet of the reservoir.41. A septum replacement kit according to claim 40, wherein the septuminstallation tool comprises a tubular member adapted for insertion intothe fluid flow inlet of the reservoir, an opening in the tubular memberfor insertion and retention of said septum therein, and a plunger memberdisposable in said tubular member for expulsion of said septum from thetubular member, wherein insertion of the septum into the tubular membercompresses the septum, and wherein expulsion of the septum from thetubular member into the fluid inlet reservoir permits the septum toexpand to fill in and seal the fluid inlet reservoir.
 42. A septumreplacement kit according to claim 40, wherein the septum is made of aself-sealing elastomeric material.